We have explored the therapeutic potential of statins in patients with different inflammatory rheumatic diseases refractory to conventional therapy. We found that simvastatin (80mg o.d. for eight days) induced a rapid and significant reduction in proteinuria levels in three systemic lupus erythematosus (SLE) patients. A similar kind of therapy had a marked beneficial effect in a patient with Wegener's granulomatosis and a patient with erythema nodosum. On the other hand, five patients with rheumatoid arthritis (RA) who received atorvastatin for eight days (20mg/day) showed reduction in C-reactive protein levels and a clinical improvement that was classified as an ACR20 response. Prior to the administration of statins, all these patients had received aggressive conventional therapy with no satisfactory response. A significant reduction in spontaneous apoptosis of peripheral blood lymphocytes and expression of CD69 and HLA-DR was observed in SLE patients after simvastatin therapy. These results prompted us to perform a pilot short-time comparative (simvastatin versus chloroquine) open clinical trial in 15 patients with RA who were receiving methotrexate as a single disease modifying antirheumatic drug with no satisfactory response. Most patients (9/10) who received simvastatin (40mg/day) showed an ACR50 or better response after eight weeks, whereas such a response was not observed in any patient (0/5) treated with chloroquine. Our preliminary results indicate that statins may be an important therapeutic tool for the treatment of inflammatory rheumatic diseases.
SummaryThe aim of this study was to assess the effect of Adalimumab on different immune parameters in patients with RA. Adalimumab was administered (40 mg every other week for 26 weeks) to eight patients with RA that were refractory to conventional drug therapy. Peripheral blood samples were obtained at days 0, 15 and 180 of Adalimumab therapy, and the following immune parameters were assessed: Number, phenotype, and function of regulatory T lymphocytes. The induction of apoptosis of immune cells and the in vitro and in vivo reactivity towards M. tuberculosis were also analysed. All patients responded to Adalimumab (ACR response 50-70), and a modest but significant increase in the number and function of regulatory T cells was observed at day 15 of anti-TNF-a a a a therapy. In addition, an increased percent of apoptotic cells was detected in the peripheral blood at day 15 of Adalimumab therapy. Unexpectedly, most of these effects were not further observed at day 180. However, two patients showed a persistent and marked reduction in the reactivity to M. tuberculosis . Although we have found that Adalimumab affects the number and function of regulatory T lymphocytes, and the apoptosis of immune cells, these effects are transient and its possible causal relationship with the therapeutic activity of this biological agent remains to be determined. Nevertheless, the down-regulatory effect of Adalimumab on the reactivity to M. tuberculosis could be related to an enhanced risk of tuberculosis reactivation.
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